title: Adhesins and host serum factors drive Yop translocation by yersinia into professional phagocytes during animal infection.
abstract: Yersinia delivers Yops into numerous types of cultured cells, but predominantly into professional phagocytes and B cells during animal infection. The basis for this cellular tropism during animal infection is not understood. This work demonstrates that efficient and specific Yop translocation into phagocytes by Yersinia pseudotuberculosis (Yptb) is a multi-factorial process requiring several adhesins and host complement. When WT Yptb or a multiple adhesin mutant strain, ΔailΔinvΔyadA, colonized tissues to comparable levels, ΔailΔinvΔyadA translocated Yops into significantly fewer cells, demonstrating that these adhesins are critical for translocation into high numbers of cells. However, phagocytes were still selectively targeted for translocation, indicating that other bacterial and/or host factors contribute to this function. Complement depletion showed that complement-restricted infection by ΔailΔinvΔyadA but not WT, indicating that adhesins disarm complement in mice either by prevention of opsonophagocytosis or by suppressing production of pro-inflammatory cytokines. Furthermore, in the absence of the three adhesins and complement, the spectrum of cells targeted for translocation was significantly altered, indicating that Yersinia adhesins and complement direct Yop translocation into neutrophils during animal infection. In summary, these findings demonstrate that in infected tissues, Yersinia uses adhesins both to disarm complement-dependent killing and to efficiently translocate Yops into phagocytes.
authors.affiliation: Tufts University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Maldonado-Arocho
authors.forename: Carlos
authors.initials: C
authors.lastname: Green
authors.forename: Michael L
authors.initials: ML
authors.lastname: Fisher
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Paczosa
authors.forename: Joan
authors.initials: J
authors.lastname: Mecsas
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010586:Phagocytes / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D021381:Protein Transport / Q000235:genetics; D015011:Yersinia pseudotuberculosis / Q000235:genetics / Q000378:metabolism*; D015012:Yersinia pseudotuberculosis Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018829:Adhesins, Bacterial; D003165:Complement System Proteins